Seldomycin factor 5 is a broad spectrum antibacterial agent which is produced by the forementation of Streptomyces hofunensis as disclosed in U.S. Pat. No. 3,939,043. The antibiotic is represented by the following structure. ##STR3##
Seldomycin factor 5 is also known as Antibiotic XK-88-5. It is a highly active, broad-spectrum antibiotic effective against both Gram-positive and Gram-negative organisms such as Staphylococcus aureus, Klebsiella pneumoniae, Escherchia coli and Proteus, species.
Seldomycin factor 5 is only one of a number of antibiotics produced by the fermentation of Streptomyces hofunensis. The isolation and characteristics of seldomycin factor 5 is described in the above referred to U.S. Pat. No. 3,939,043 and the elucidation of its structure is described in the Journal of Antibiotics 30 pp 39-49 (1977).
Seldomycin factor 5 is an aminoglycoside antibiotic and the aminoglycoside antibiotics are a valuable therapeutic class of antibiotics which includes the kanamycins, streptomycins, gentamicins and fortimicins. While the naturally produced parent antibiotic are valuable, broad spectrum antibiotics, it has been found that chemical modification of the parent structures results in improved entities either by improving the intrinsic activity, improving the activity against resistant strains, or reducing the toxicity. Further, because of the development of aminoglycoside-resistant strains and inactiviation of the parent antibiotics by R-mediated factors which can develop, the search for new entities continues which are either improved in one of the above-metioned ways or in providing reserve antibiotics which have useful activity.
A number of chemical modifications have been made in the seldomycin factor 5 structure. Those modifications have resulted in 3'-epi-seldomycin factor 5, 6'-N-alkylseldomycin factor 5 derivatives, 3'-deoxyseldomycin factor 5 and 1-N-acyl-seldomycin factor 5 derivatives among others. The above derivatives are the subject of pending United States patent applications and issued patents. 1-N-alkylseldomycin factor 5 derivatives are disclosed in U.S. Pat. No. 4,002,608.
The present invention provides a potent class of seldomycin factor 5 derivatives, O-demethylseldomycin factor 5 derivatives.